Partition distribution of selected organochlorine pesticides in water, sediment pore water and surface sediment from uMngeni River, KwaZulu-Natal, South Africa

Abstract: Organochlorine pesticides (OCPs) were analysed in surface water, pore water and surface sediment samples collected from the uMngeni River, which is one of the largest rivers in the province of KwaZulu-Natal, South Africa. Liquid-liquid extraction was used to extract the analytes from water and pore water samples and soxhlet extraction was used to extract sediment samples with subsequent florisil clean-up and gas chromatography-mass spectrometry (GC-MS) analysis. Twelve selected OCPs were analysed and their total concentrations were found to range from 8.04–21.06 ng/mL, 36.06–188.43 ng/mL and 148.17–554.73 ng/g in unfiltered surface water, unfiltered pore water and surface sediment (dry weight (dw)), respectively. The results indicated that the concentrations of these selected pesticides were far higher in sediment (72%) than in pore water (25%) and water (3%). The most polluted sites were Northern Wastewater Treatment influent (NWTI) for water (Σ12OCP = 19.41 ± 1.43 ng/mL) and Northern Wastewater Treatment effluent (NWTE) for pore water (Σ12 OCP = 166.23 ± 7.16 ng/mL) and sediment (Σ12 OCP = 495.21 ± 32.38 ng/g). The most abundant individual OCPs and their average concentrations in general in the river were p,p′-DDE in unfiltered water (1.62 ±0.22 ng/mL) and unfiltered sediment pore water (17.09 ±7.96 ng/mL), and endrin in surface sediment (55.57 ± 19.01 ng/g, dw)

Determinants of antibody persistence across doses and continents after single-dose rVSV-ZEBOV vaccination for Ebola virus disease: an observational cohort study.

BACKGROUND: The recombinant vesicular stomatitis virus (rVSV) vaccine expressing the Zaire Ebola virus (ZEBOV) glycoprotein is efficacious in the weeks following single-dose injection, but duration of immunity is unknown. We aimed to assess antibody persistence at 1 and 2 years in volunteers who received single-dose rVSV-ZEBOV in three previous trials. METHODS: In this observational cohort study, we prospectively followed-up participants from the African and European phase 1 rVSV-ZEBOV trials, who were vaccinated once in 2014-15 with 300 000 (low dose) or 10-50 million (high dose) plaque-forming units (pfu) of rVSV-ZEBOV vaccine to assess ZEBOV glycoprotein (IgG) antibody persistence. The primary outcome was ZEBOV glycoprotein-specific IgG geometric mean concentrations (GMCs) measured yearly by ELISA compared with 1 month (ie, 28 days) after immunisation. We report GMCs up to 2 years (Geneva, Switzerland, including neutralising antibodies up to 6 months) and 1 year (Lambaréné, Gabon; Kilifi, Kenya) after vaccination and factors associated with higher antibody persistence beyond 6 months, according to multivariable analyses. Trials and the observational study were registered at ClinicalTrials.gov (Geneva: NCT02287480 and NCT02933931; Kilifi: NCT02296983) and the Pan-African Clinical Trials Registry (Lambaréné PACTR201411000919191). FINDINGS: Of 217 vaccinees from the original studies (102 from the Geneva study, 75 from the Lambaréné study, and 40 from the Kilifi study), 197 returned and provided samples at 1 year (95 from the Geneva study, 63 from the Lambaréné, and 39 from the Kilifi study) and 90 at 2 years (all from the Geneva study). In the Geneva group, 44 (100%) of 44 participants who had been given a high dose (ie, 10-50 million pfu) of vaccine and who were seropositive at day 28 remained seropositive at 2 years, whereas 33 (89%) of 37 who had been given the low dose (ie, 300 000 pfu) remained seropositive for 2 years (p=0·042). In participants who had received a high dose, ZEBOV glycoprotein IgG GMCs decreased significantly between their peak (at 1-3 months) and month 6 after vaccination in Geneva (p0·05). Neutralising antibodies seem to be less durable, with seropositivity dropping from 64-71% at 28 days to 27-31% at 6 months in participants from the Geneva study. INTERPRETATION: Antibody responses to single-dose rVSV-ZEBOV vaccination are sustained across dose ranges and settings, a key criterion in countries where booster vaccinations would be impractical. FUNDING: The Wellcome Trust and Innovative Medicines Initiative 2 Joint Undertaking

Piperidinols that show anti-tubercular activity as inhibitors of arylamine N-acetyltransferase: an essential enzyme for mycobacterial survival inside macrophages

Latent M. tuberculosis infection presents one of the major obstacles in the global eradication of tuberculosis (TB). Cholesterol plays a critical role in the persistence of M. tuberculosis within the macrophage during latent infection. Catabolism of cholesterol contributes to the pool of propionyl-CoA, a precursor that is incorporated into cell-wall lipids. Arylamine N-acetyltransferase (NAT) is encoded within a gene cluster that is involved in the cholesterol sterol-ring degradation and is essential for intracellular survival. The ability of the NAT from M. tuberculosis (TBNAT) to utilise propionyl-CoA links it to the cholesterol-catabolism pathway. Deleting the nat gene or inhibiting the NAT enzyme prevents intracellular survival and results in depletion of cell-wall lipids. TBNAT has been investigated as a potential target for TB therapies. From a previous high-throughput screen, 3-benzoyl-4-phenyl-1-methylpiperidinol was identified as a selective inhibitor of prokaryotic NAT that exhibited antimycobacterial activity. The compound resulted in time-dependent irreversible inhibition of the NAT activity when tested against NAT from M. marinum (MMNAT). To further evaluate the antimycobacterial activity and the NAT inhibition of this compound, four piperidinol analogues were tested. All five compounds exert potent antimycobacterial activity against M. tuberculosis with MIC values of 2.3-16.9 µM. Treatment of the MMNAT enzyme with this set of inhibitors resulted in an irreversible time-dependent inhibition of NAT activity. Here we investigate the mechanism of NAT inhibition by studying protein-ligand interactions using mass spectrometry in combination with enzyme analysis and structure determination. We propose a covalent mechanism of NAT inhibition that involves the formation of a reactive intermediate and selective cysteine residue modification. These piperidinols present a unique class of antimycobacterial compounds that have a novel mode of action different from known anti-tubercular drugs

Controlled Human Malaria Infection in Semi-Immune Kenyan Adults (CHMI-SIKA): a study protocol to investigate in vivo Plasmodium falciparum malaria parasite growth in the context of pre-existing immunity [version 2; peer review: 2 approved]

Malaria remains a major public health burden despite approval for implementation of a partially effective pre-erythrocytic malaria vaccine. There is an urgent need to accelerate development of a more effective multi-stage vaccine. Adults in malaria endemic areas may have substantial immunity provided by responses to the blood stages of malaria parasites, but field trials conducted on several blood-stage vaccines have not shown high levels of efficacy. We will use the controlled human malaria infection (CHMI) models with malaria-exposed volunteers to identify correlations between immune responses and parasite growth rates in vivo. Immune responses more strongly associated with control of parasite growth should be prioritized to accelerate malaria vaccine development. We aim to recruit up to 200 healthy adult volunteers from areas of differing malaria transmission in Kenya, and after confirming their health status through clinical examination and routine haematology and biochemistry, we will comprehensively characterize immunity to malaria using >100 blood-stage antigens. We will administer 3,200 aseptic, purified, cryopreserved Plasmodium falciparum sporozoites (PfSPZ Challenge) by direct venous inoculation. Serial quantitative polymerase chain reaction to measure parasite growth rate in vivo will be undertaken. Clinical and laboratory monitoring will be undertaken to ensure volunteer safety. In addition, we will also explore the perceptions and experiences of volunteers and other stakeholders in participating in a malaria volunteer infection study. Serum, plasma, peripheral blood mononuclear cells and whole blood will be stored to allow a comprehensive assessment of adaptive and innate host immunity. We will use CHMI in semi-immune adult volunteers to relate parasite growth outcomes with antibody responses and other markers of host immunity. / Registration: ClinicalTrials.gov identifier NCT02739763

Hall Measurements on Carbon Nanotube Paper Modified With Electroless Deposited Platinum

Carbon nanotube paper, sometimes referred to as bucky paper, is a random arrangement of carbon nanotubes meshed into a single robust structure, which can be manipulated with relative ease. Multi-walled carbon nanotubes were used to make the nanotube paper, and were subsequently modified with platinum using an electroless deposition method based on substrate enhanced electroless deposition. This involves the use of a sacrificial metal substrate that undergoes electro-dissolution while the platinum metal deposits out of solution onto the nanotube paper via a galvanic displacement reaction. The samples were characterized using SEM/EDS, and Hall-effect measurements. The SEM/EDS analysis clearly revealed deposits of platinum (Pt) distributed over the nanotube paper surface, and the qualitative elemental analysis revealed co-deposition of other elements from the metal substrates used. When stainless steel was used as sacrificial metal a large degree of Pt contamination with various other metals was observed. Whereas when pure sacrificial metals were used bimetallic Pt clusters resulted. The co-deposition of a bimetallic system upon carbon nanotubes was a function of the metal type and the time of exposure. Hall-effect measurements revealed some interesting fluctuations in sheet carrier density and the dominant carrier switched from N- to P-type when Pt was deposited onto the nanotube paper. Perspectives on the use of the nanotube paper as a replacement to traditional carbon cloth in water electrolysis systems are also discussed

Synthesis of an ordered mesoporous carbon with graphitic characteristics and its application for dye adsorption

An ordered mesoporous carbon (OMC) was prepared by a chemical vapor deposition technique using liquid petroleum gas (LPG) as the carbon source. During synthesis, LPG was effectively adsorbed in the ordered mesopores of SBA-15 silica and converted to a graphitic carbon at 800 °C. X-ray diffraction and nitrogen adsorption/desorption data and high-resolution transmission electron microscopy (HRTEM) of the OMC confirmed its ordered mesoporous structure. The OMC was utilized as an adsorbent in the removal of dyes from aqueous solution. A commercial powder activated carbon (AC) was also investigated to obtain comparative data. The efficiency of the OMC for dye adsorption was tested using acidic dye acid orange 8 (AO8) and basic dyes methylene blue (MB) and rhodamine B (RB). The results show that adsorption was affected by the molecular size of the dye, the textural properties of carbon adsorbent and surface-dye interactions. The adsorption capacities of the OMC for acid orange 8 (AO8), methylene blue (MB) and rhodamine B (RB) were determined to be 222, 833, and 233 mg/g, respectively. The adsorption capacities of the AC for AO8, MB, and RB were determined to be 141, 313, and 185 mg/ g, respectively. The OMC demonstrated to be an excellent adsorbent for the removal of MB from wastewater.Web of Scienc

Malaria is a cause of iron deficiency in African children

Malaria and iron deficiency (ID) are common and interrelated public health problems in African children. Observational data suggest that interrupting malaria transmission reduces the prevalence of ID1. To test the hypothesis that malaria might cause ID, we used sickle cell trait (HbAS, rs334), a genetic variant that confers specific protection against malaria2, as an instrumental variable in Mendelian randomization analyses. HbAS was associated with a 30% reduction in ID among children living in malaria-endemic countries in Africa (n = 7,453), but not among individuals living in malaria-free areas (n = 3,818). Genetically predicted malaria risk was associated with an odds ratio of 2.65 for ID per unit increase in the log incidence rate of malaria. This suggests that an intervention that halves the risk of malaria episodes would reduce the prevalence of ID in African children by 49%

Functional Memory B Cells and Long-Lived Plasma Cells Are Generated after a Single Plasmodium chabaudi Infection in Mice

Antibodies have long been shown to play a critical role in naturally acquired immunity to malaria, but it has been suggested that Plasmodium-specific antibodies in humans may not be long lived. The cellular mechanisms underlying B cell and antibody responses are difficult to study in human infections; therefore, we have investigated the kinetics, duration and characteristics of the Plasmodium-specific memory B cell response in an infection of P. chabaudi in mice. Memory B cells and plasma cells specific for the C-terminal region of Merozoite Surface Protein 1 were detectable for more than eight months following primary infection. Furthermore, a classical memory response comprised predominantly of the T-cell dependent isotypes IgG2c, IgG2b and IgG1 was elicited upon rechallenge with the homologous parasite, confirming the generation of functional memory B cells. Using cyclophosphamide treatment to discriminate between long-lived and short-lived plasma cells, we demonstrated long-lived cells secreting Plasmodium-specific IgG in both bone marrow and in spleens of infected mice. The presence of these long-lived cells was independent of the presence of chronic infection, as removal of parasites with anti-malarial drugs had no impact on their numbers. Thus, in this model of malaria, both functional Plasmodium-specific memory B cells and long-lived plasma cells can be generated, suggesting that defects in generating these cell populations may not be the reason for generating short-lived antibody responses